Lung-lect-5&6

Pulmonary Tuberculosis

Epidemiology: Common disease infects more than 3 millions

per year around the world and about one third of world’s population is infected and regarded as the single most important infectious cause of death on earth.

It increased now in western countries in AIDS patients.

Multi-drug resistance strains.Very resistant pathogenUnusual lipids in membrane

Survives drying out for weeks in sputumResistant to chemical disinfectants &

antisepticsPathogenicity dependent on immune

system of hostInhaled bacilli may be digested by

macrophages

Etiology and pathogenesis The route of infection differ according to

species, M tuberculosis by inhalation of droplets, while bovis by ingestion of unpasteurized milk of infected cow.

Now there is species of no virulence in normal host but cause disseminated disease in 15-24% of AIDS patients.

M. is aerobic, non spore forming, non motile bacilli with waxy coat give the red dye in acid fast stain.

Its growth in culture is very slow 4-6 weeks. Tuberculin test by subcutaneous injection of

purified protein derivatives of M. tub. Can confirm previous exposure to the bacteria and not active infection.

Currently molecular technique now give rapid diagnostic tools.

Important considerations in Pathogenesis

1- the basis of virulence of the organism. 2- the relationship with hypersensitivity. 3- tissue destruction and caseous

necrosis.

1- VIRULENCE: It has no exotoxin or endotoxin or enzyme, but its Pathogenicity is related to its ability to escape killing by macrophages and its role in induction of delayed hypersensitivity reaction by wall components: 1- Cord factor: found in virulent strains and cause growth of bacilli in serpentine cords in vitro and has role in granuloma formation in vivo.2- Sulfatides: also in virulent strain can prevent fusion of phagosomes of macrophages containing bacilli with the lysosomes.3- LAM: has many effects: a- inhibits macrophage activation by interferon-gamma, and, b- induces macrophages to secrete TNF alpha which causes weight loss, fever and tissue damage, and to secrete IL-10 which suppresses T cell proliferation.

4- Heat shock protein: Highly immunogenic causes autoimmune reactions.

5- Complement activation: on the surface of the mycobacterium which facilitates its uptake by macrophages without killing it.

The development of delayed type IV hypersensitivity reaction:

Initial exposure causes non specific inflammatory response.

In 2-3 weeks there is development of granulomatous reaction with central caseation and soft tubercle.

The host response depends on whether infection is a first exposure or a secondary reaction in already sensitized host, and this explain the emergence of resistance to infection and tissue destructiveness.

begins with the inhalation of the m.o. and ends by the development of T cell mediated immune response which controls up to 95% of the cases. The inhaled m.o. is phagocytosed by alveolar macrophages, multiply and lyses the cell result in dissemination of the infection.After few weeks T cell mediated immunity developed. (+PDD).

Pathogenesis of Primary mycobacterium tuberculosis:

Pathogenesis of primary TB contd:. This process started by secretion of interferon Gamma by

CD4+ T- helper cells, that activate macrophages to kill intracellular m.o., via reactive nitrogen intermediates, including No, No2, and HNo3.

This is associated by the formation of epithelioid granulomas.

Also there is killing of mycobacterium infected macrophages by CD8+ T lymphocytes. This result in formation of caseous material in the center of the granulomas which is directly toxic to the mycobacterium that can not grow in acidic media lacking oxygen result in control of infection.

This is ultimately scarred and calcified in the lung and the associated LN infected in primary Ghon complex.

Pathogenesis: SECONDARY TUBERCULOSIS: EITHER: 1- Re-infection. 2- Re-activation of dormant

disease. 3- progress directly from primary lesions. This occur either due to virulent strain or susceptible

host. This is proved by detection of specific gene Bcg in mice which encode for membrane transport protein, that interfere with killing m.o.

Granulomas of secondary infection most often occur in the apex of the lungs or widely disseminate in the lungs, kidneys, meninges, marrow and other organs, and this reflects the failure of the body to control the infection due to tissue damage, granuloma formation and caseation as a reflection of delayed type HSR.

Explanation of this by destruction and cavity formation, rupture into blood vessels and dissemination to the body or into bronchus releasing infection into air.

Spread of TB to other tissues

Spreading of pathogen via lymph, blood or airwaysContralateral lungPleural surfaceBrain, bone, urogenital tractGI-tract

Pulmonary Tuberculosis

morphology

MORPHOLOGY Primary pulmonary tuberculosis: seen as initial

focus of primary infection known as Gohn focus that is seen in the parenchyma of the lung mainly sub-pleural just below the inter-lobar fissure between the upper and the lower lobes (middle). Also known as Gohn complex if associated with enlarged caseous lymph node draining the parenchymal focus.

In most cases the disease is asymptomatic and the lesions fibrosed and calcified, but in infants, children and immuno-deficient adults progressive spread with cavitations, tuberculous pneumonia or miliary tuberculosis may follow.

Pulmonary Tuberculosis

Primary infection leads to Ghon complex with Granuloma formation which later heals resulting in calcification (X-ray)

Often followed by secondary infection

SECONDARY TUBERCULOSIS Mor: Patterns of secondary tuberculosis: 1- localized apical lesion. 2- Endo-bronchial, Endo-tracheal. 3- Cavitary. 4- Advanced. 5- By lymphatics to vena cava and cause

pulmonary miliary tuberculosis. 6- By pulmonary veins cause systemic miliary

TB. 7- Isolated organ lesion.

SECONDARY TUBERCULOSIS: GROSS: Can result form reactivation of the old lesions,

possible sub-clinical infection and established in high oxygen tension, particularly the lung apices.

It begins as a small focus of consolidation less than 3 cm, but less commonly may be located in other regions of the lung as the hilus and associated with lymph node enlargement .

The usual course start as small area of caseation that does not cavitate, because it fails to communicate with the bronchus or bronchiole result in progressive fibrous encapsulation and calcification.

This may progress to see coalescent tubercles to create confluent area of consolidation.

Also may be converted to fibrocalcific scar.

MICROSCOPY : Coalescent granulomas with central caseation

(epithelioid cells aggregates surrounded by area of fibroblasts and lymphocytes with Langhan’s giant cells). The central caseation looks homogenous Eosinophilic material.

The residual caseous debris becomes totally and heavily walled off by hyaline connective issue and the multinucleated giant cells disappear,

Also may heal spontaneously or with therapy resulting in a fibrocalcific nodule or may progress to PROGRESSIVE PULMONARY TB.

PROGRESSIVE pulmonary tuberculosis:

Active lesions continue to progress causing further pulmonary and even distant organ involvement result in different Clinico-pathologic consequences.

1- Cavitary fibro-caseous tuberculosis (apical and advanced).

2- miliary tuberculosis. 3- Tuberculous bronchopneumonia.

Cavitary fibro-caseous tuberculosis: Erosion into a bronchiole lead to drainage and cavity

formation and with the increased oxygen tension lead to increase growth of bacilli.

The cavity is lined by a yellow gray caseous material and walled off by a fibrous tissue.

The disease may disseminate through airways to other parts in the lung or upper respiratory tract.

Also may spread to lymphatics to other areas of lungs that cause pulmonary miliary tuberculosis.

This may affect one lobe or more and even involve the pleura causing pleural effusion.

Pulmonary Tuberculosis –Sever Form X-ray

morphology

Miliary tuberculosis: Occur as a result of diffuse involvement of the

lung or the organs of the body like, spleen, liver, bone marrow, retina ..etc.

The organ will be studded by many tubercles, small in size, vary, and solid white with caseous granulomas seen in it microscopically.

Sometimes isolated organ involvement occur by clearing of the m.o. in the organs and stay in one organ causing tuberculous lesion in it as the kidney, adrenals and testes.

Tuberculous bronchopneumonia:

The infection may spread rapidly throughout large areas of the lung leading to diffuse bronchopneumonia or lobar exudative consolidation.